New multifunctional, degradable, polymeric biomaterial systems are needed that can be tailored to specific cell and tissue needs in vitro and in vivo. While protein-protein composites dominate tissue structure and function in our bodies, we have been unable to recapitulate the complexity and control of such systems in vitro for new biomaterials in order to direct cell and tissue functions. For example, material systems that can form mechanically robust and durable biomaterials to give highly flexible and dynamic biomaterials, remains a challenge. Our goal is to construct a panel of composite protein biomaterials that can cover a range of physical properties, to mimic the elasticity of diverse tissue structures and the consequential ability to control biological function - such as to direct stem cell responses. The hypothesis is that combinations of a highly elastic and dynamic structural protein (tropoelastin) with tough, durable proteins (silk) will generate new multifunctional protein composite systems that can offer a broad platform of utility to the biomaterials field. We propose to generate a new family of highly controllable composite fibrous protein systems, based on combinations of these two well-established structural proteins, tropoelastin and silk, both biodegradable protein polymers with good biocompatibility. These proteins encompass a range of biomaterial needs; tropoelastin provides highly flexible and dynamic structural features, silk provides mechanical toughness and slow degradation. Our findings of molecular-scale interactions between these two structural proteins, forms the basis of the present proposal. The experimental plans are focused on: (a) further elucidation of the mechanistic interactions between tropoelastin and silk to optimize control of material structure and function, (b) assessment of cell interactions for the range of materials generated to understand relationships between the protein composites, material compliance and cell outcomes, using hMSCs and cortical neurons, and in vivo screens of material degradation profiles and inflammatory responses, and (c) exploitation of the dynamic material properties achievable with these systems towards support of cell functions in vitro. The experimental plans are supported by extensive preliminary data that demonstrate our ability to generate the required materials (tropoelastin, silks), to functionalize the materials (e.g., surface chemistry),to probe the interactions among the two components with mechanistic insight, to process the proteins into new material formats, and to direct cell outcomes on these materials with outcomes dependent on the composition. The overall outcome from the plans would be a new protein composite biomaterials platform that would fill an important need in the field of biomaterials, with direct relevance to tough but flexible systems and strong, durable systems.